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Investigation of Potential Factors t...

Allen, Shannon Alexis.

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Investigation of Potential Factors that Mediate the Sexual Transmission of HIV.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Investigation of Potential Factors that Mediate the Sexual Transmission of HIV./
作者:	Allen, Shannon Alexis.
面頁冊數:	150 p.
附註:	Source: Dissertation Abstracts International, Volume: 77-02(E), Section: B.
Contained By:	Dissertation Abstracts International77-02B(E).
標題:	Molecular biology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3724165
ISBN:	9781339075907

Investigation of Potential Factors that Mediate the Sexual Transmission of HIV.
Allen, Shannon Alexis.

Investigation of Potential Factors that Mediate the Sexual Transmission of HIV. - 150 p.

Source: Dissertation Abstracts International, Volume: 77-02(E), Section: B.

Thesis (Ph.D.)--Northwestern University, 2015.

Human immunodeficiency (HIV) transmission events occur in women when semen harboring infectious virus is deposited onto the female genital mucosa. A successful infection requires that virus must first transverse the mucus layer that blankets the mucosa before penetrating the vaginal, ectocervical and endocervical epithelia to infect target cells. Seminal factors such as semen-derived enhancer of virus infection (SEVI) fibrils were previously shown to greatly enhance the infectivity of HIV in cell-culture systems. Yet, when SEVI was intravaginally applied to the genital tracts of female rhesus macaques, vaginal transmission rates were unaffected. To define how SEVI might function in the context of sexual transmission, we applied HIV and SEVI to intact human and macaque reproductive tract tissues to determine how it influences virus interactions with these mucosal barriers. We show that SEVI binds HIV and sequesters most virions to the luminal surface of the ectocervical epithelium significantly reducing the number of virions that penetrated the tissue. In the endocervical simple columnar epithelium, SEVI was no longer fibrillar in structure and was detached from virions but allowed a small but significantly deeper epithelial virus penetration. These observations reveal that the action of SEVI in intact tissues is different in the anatomical context of sexual transmission and may explain the lack of stimulation of infection observed in macaque mucosal transmission models.

ISBN: 9781339075907Subjects--Topical Terms:

517296
Molecular biology.

Investigation of Potential Factors that Mediate the Sexual Transmission of HIV.
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245 1 0 $a Investigation of Potential Factors that Mediate the Sexual Transmission of HIV.
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500 $a Adviser: Thomas J. Hope.
502 $a Thesis (Ph.D.)--Northwestern University, 2015.
520 $a Human immunodeficiency (HIV) transmission events occur in women when semen harboring infectious virus is deposited onto the female genital mucosa. A successful infection requires that virus must first transverse the mucus layer that blankets the mucosa before penetrating the vaginal, ectocervical and endocervical epithelia to infect target cells. Seminal factors such as semen-derived enhancer of virus infection (SEVI) fibrils were previously shown to greatly enhance the infectivity of HIV in cell-culture systems. Yet, when SEVI was intravaginally applied to the genital tracts of female rhesus macaques, vaginal transmission rates were unaffected. To define how SEVI might function in the context of sexual transmission, we applied HIV and SEVI to intact human and macaque reproductive tract tissues to determine how it influences virus interactions with these mucosal barriers. We show that SEVI binds HIV and sequesters most virions to the luminal surface of the ectocervical epithelium significantly reducing the number of virions that penetrated the tissue. In the endocervical simple columnar epithelium, SEVI was no longer fibrillar in structure and was detached from virions but allowed a small but significantly deeper epithelial virus penetration. These observations reveal that the action of SEVI in intact tissues is different in the anatomical context of sexual transmission and may explain the lack of stimulation of infection observed in macaque mucosal transmission models.
520 $a It has been suggested that certain forms of contraception, such as the progesterone-based Depo-Provera, may increase the risk of HIV infection in women. Contraceptives alter mucus consistency such that it becomes impenetrable to sperm; however, it is not known how these changes might affect the interaction of HIV with mucus. To study the effects of various contraceptives on HIV mobility, we quantified the diffusion of HIV in the mucus of women initiating Mirena, Depo-Provera or NuvaRing and primates exposed to Depo-Provera and Alesse. Particles were tracked using custom-based tracking algorithms and the mean-squared displacement was calculated. We found that HIV mobility is enhanced with Depo-Provera. Mirena and NuvaRing reduced viral transport while Alesse did not alter particle transport. Our results provide direct mechanistic insight that links HC use to HIV-risk.
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